Dehydroepiandrosterone (DHEA) also known as androstenolone or prasterone or 3β-hydroxyandrost-5-en-17-one or 5-androsten-3β-ol-17-one, is an important endogenous steroid hormone and has the structure of formula (I).

Dehydroepiandrosterone (DHEA) is a key intermediate in the synthesis of steroidal molecules, including but not limited to abiraterone acetate, a drug used in the treatment of castration-resistant prostate cancer.
An article by J. Bryan Jones et al., “Steroids and steroidases.VI. On the C-17 specificity of the Δ5-3-ketoisomerase of Psudomonas testosterone and evidence for substrate micelle formation,” Candian Journal of Chemistry, 46,1459-1465 (1968) describes a process for the preparation of androst-5-ene-3,17-dione, an intermediate used for the preparation of DHEA. The process disclosed in the said reference involves reacting androst-4-ene-3,17-dione with potassium t-butoxide in t-butyl alcohol under nitrogen atmosphere for 90 minutes at 20° C., followed by quenching the reaction mass by rapid addition of 10% aqueous acetic acid, adding excess sodium bicarbonate, extracting with ether, evaporating at room temperature and recrystallization from acetone to give androst-5-ene-3,17-dione.
However, the above process is disadvantageous in that, it involves the use of higher amounts of base i.e., 10 equivalents of potassium tert-butoxide, results in the formation of oxidized impurities of androst-5-ene-3,17-dione and has workup procedure which may not suitable on an industrial scale and thereby results in low and unsatisfactory yields.
Accordingly, there remains a need to provide improved processes for preparing androst-5-ene-3,17-dione that eliminates and reduces the drawbacks of the prior art in a convenient manner.
Chinese Patent Application Publication No. 102212099 disclose a multi-step process for the preparation of dehydroepiandrosterone starting from 16-dehydropregnenolone acetate and involves the reaction steps as depicted in Scheme 1 below.

Chinese Patent Application Publication No. 102603841 disclose a multi-step process for the preparation of dehydroepiandrosterone from 4-androsten-3,17-dione, and involves the reaction steps as depicted in Scheme 2 below.

Chinese Patent Application Publication No. 102603839 describes a multi-step synthetic process for preparation of dehydroepiandrosterone starting from 16-dehydropregnenolone acetate, which involves (i) preparation of 16-dehydropregnenolone acetate oxime (ii) Beckmann rearrangement of 16-dehydropregnenolone acetate oxime to obtain dehydroepiandrosterone acetate (iii) hydrolysis of dehydroepiandrosterone acetate to give dehydroepiandrosterone. The reaction steps of the said process are depicted in Scheme 3 below.

Chinese Patent Application Publication No. CN 101362789 and 101717422, Korean patent application Publication No. 2004040555 also discloses synthetic processes for the preparation of dehydroepiandrosterone.
The above described synthetic processes for the preparation of dehydroepiandrosterone includes multiple steps, and a sequence of protection/deprotection steps in order to achieve a stereo- and regioselective reduction at position C3 and may not be suitable for commercial scale synthesis.
Mamoli et al., in U.S. Pat. No. 2,186,906 describes biochemical hydrogenation process for the conversion of a keto-compound of the cyclopentano-10,13-dimethyl-poly-hydro-phenanthrene series (Δ4,5-androstendione) into a corresponding hydroxyl compound of the same series (Δ4,5-androstenole-17-one-3) which comprises subjecting such keto compound to the action of a reducing yeast-containing fermentation solution.
Misaki et al., in U.S. Pat. No. 4,791,057 describes highly sensitive quantitative assay method for a component (which is a 3β-hydroxysteroid or a 3-ketosteroid) in a specimen to be assayed, which involves the steps of causing this component in the specimen to take part in the 3β-hydroxysteroid & 3-ketosteroid cycling reaction and measuring a detectable change in the reaction system comprising a 3β-hydroxysteroid oxidase and or 3β-hydroxysteroid dehydrogenase. In the cycling reaction, 3β-hydroxysteroid oxidase consumes O2 and converts 3-hydroxy steroid to a 3-ketosteroid, 3β-hydroxysteroid dehydrogenase in the presence of reduced NAD(P)+ converts 3-ketosteroid to a 3-hydroxy steroid and generate NAD(P). The 3β-hydroxysteroid & 3-ketosteroid cycling reaction described in the said patent is schematically represented in Scheme 4 below:

Though the above references discloses a enzymatic conversion of 3-hydroxy steroid to 3-keto steroids or vice-versa, they do not disclose a process for the preparation of dehydroepiandrosterone and there remains a complex challenge in developing an improved process which displays required regioselectivity by reducing the 3-oxo group of the steroid leaving the 17-oxo group intact and stereoselectivity by producing the corresponding 3β-hydroxy compound.
The process according to the present application relates to an enzymatic process for the preparation of dehydroepiandrosterone. The enzymatic reduction process of the present application is eco-friendly, cost-effective and commercially viable.